102例先天性甲状腺功能减低症甲状腺发育不良相关基因突变检测

Mutation detection of thyroid dysgenesis related genes in 102 Chinese patients with congenital hypothyroidism

目的对102例先天性甲状腺功能减低症患儿进行甲状腺发育不良相关基因促甲状腺激素受体(TSHR)、PAX8、NKX2-1、NKX2-5、FOXE-2基因突变分析。方法对102例先天性甲状腺功能减低症患儿采外周血并提取DNA,用wafergen验证检测患儿促甲状腺激素受体(TSHR)、PAX8、NKX2-1、NKX2-5、FOXE-2基因突变。PCR扩增患儿甲状腺发育不良相关基因突变位点所在的基因序列,以DNA测序技术检测基因突变。结果发现5种TSHR基因突变c.154C>A[p.Pro52Thr]、c.394G>C[p.Gly132Arg]、c.2066T>G[p.Val689Gly]、c.1576G>A[p.Ala526Thr]和c.2272G>A[p.Glu758Lys],2种PAX8基因单核苷酸多态性位点(SNP)rs189229644和rs200138601,未检测到PAX8、NKX2-1、NKX2-5和FOXE-2基因突变。结论中国人群先天性甲状腺功能减低症患儿存在较高频率的促甲状腺激素受体基因突变,值得进一步开展深入研究。

Objective:To identify thyroid dysgenesis related genes mutations in 102 Chinese patients with congenital hypothyroidism. Methods:Genomic DNA was isolated from the peripheral blood samples of 102 Chinese patients.TSH receptor(TSHR)gene,PAX8 gene,NKX2-1 gene,NKX2-5 gene and FOXE-2 gene mutations were detected by wafergen technique.DNA sequence of these gene mutations were amplified by PCR,then the PCR products were sequenced bi-directionally.Results:We found five TSHR gene mutations including c.154 C>A [p.Pro52 Thr],c.394 G>C [p.Gly132 Arg],c.2066 T>G [p.Val689 Gly],c.1576 G>A[p.Ala526 Thr] and c.2272 G>A[p.Glu758 Lys],two SNP of PAX8 gene(rs189229644,rs200138601)and no gene mutation in PAX8 gene,NKX2-1 gene,NKX2-5 gene and FOXE-2 gene. Conclusion:High frequency mutation in TSHR gene was detected in Chinese congenital hypothyroidism patients. It was worthwhile to further study the TSHR gene mutations.